Engineered Chimeric Antigen Receptor (CAR) Microglia-Like Cells for the Treatment of Neurodegenerative Disorders
AssigneeThe Trustees of the University of Pennsylvania
InventorsMatias Porras-Paniagua, Saar Gill, Frederick Bennett
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Abstract
The present disclosure provides compositions and methods comprising chimeric antigen receptors (CARs) specific for amyloid beta (Aβ) and/or Tau. In certain embodiments, the CARs do not comprise an intracellular domain. Methods of treatment are also disclosed herein.
Claims51
A chimeric antigen receptor (CAR) comprising an antigen-binding domain and a transmembrane domain, wherein the antigen binding domain comprises a heavy chain variable region (VH) comprising three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3), and a light chain variable region (VL) comprising three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), further wherein:
- (i) the antigen-binding domain binds amyloid beta (Aβ) and the CAR further comprises an intracellular domain;
- (ii) the antigen-binding domain binds Aβ and the CAR does not comprise an intracellular domain;
- (iii) the antigen-binding domain binds Tau and the CAR further comprises an intracellular domain;
- or
- (iv) the antigen-binding domain binds Tau and the CAR does not comprise an intracellular domain.
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A method of treating a neurodegenerative disease in a subject in need thereof, the method comprising:
- administering to the subject a therapeutically effective amount of a composition comprising a cell comprising a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain that binds amyloid beta, and wherein the CAR does not comprise an intracellular domain, and
- wherein the cell is a monocyte, macrophage, dendritic cell, or stem cell;
- optionally wherein the method further comprises depleting the endogenous microglia in the subject prior to the administering.
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Dependencies are inferred from the claim text.